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Introduction As an emerging infectious disease, the clinical and virologic course of coronavirus disease 2019 (COVID-19) require better investigation. The aim of the present study is to identify potential risk factors associated with persistent positive nasopharyngeal swab real-time reverse transcription polymerase chain reaction (RT-PCR) tests in a large sample of patients who recovered from COVID-19. Methods After the acute phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic infection, the Fondazione Policlinico A. Gemelli IRCSS of Rome established a post-acute care service for patients discharged from the hospital and recovered from COVID-19. Between April 21 and May 21, 2020, a total of 137 individuals who officially recovered from COVID-19 were enrolled in the present study. All patients were tested for the SARS-CoV-2 virus with nucleic acid RT-PCR tests. Analysis was conducted in June 2020. Results Of the 131 patients who repeated the nasopharyngeal swab, 22 patients (16.7%) tested positive again. Some symptoms such as fatigue (51%), dyspnea (44%), and coughing (17%) were still present in a significant percentage of patients, with no difference between patients with a negative test compared to those who tested positive. The likelihood of testing positive for SARS-CoV-2 infection was significantly higher among participants with persistent sore throat (prevalence ratio=6.50, 95% CI=1.38, 30.6) and symptoms of rhinitis (prevalence ratio=3.72, 95% CI=1.10, 12.5). Conclusions This study is the first to provide a given rate of patients (16.7%) who test positive on RT-PCR test for SARS-CoV-2 nucleic acid after recovering from COVID-19. These findings suggest that a significant proportion of recovered COVID-19 patients still could be potential carriers of the virus. In particular, if patients continue to have symptoms related to COVID-19, such as sore throat and rhinitis, it is reasonable to be cautious by avoiding close contact, wearing a face mask, and possibly repeating a nasopharyngeal swab.

Background Cell entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) depends on binding of the viral spike (S) proteins to angiotensin-converting enzyme 2 and on S protein priming by TMPRSS2. Inhibition of TMPRSS2 may work to block or decrease the severity of SARS-CoV-2 infections. Intriguingly, TMPRSS2 is an androgen-regulated gene that is up-regulated in prostate cancer where it supports tumor progression and is involved in a frequent genetic translocation with the ERG gene. First- or second-generation androgen-deprivation therapies (ADTs) decrease the levels of TMPRSS2. Here we put forward the hypothesis that ADTs may protect patients affected by prostate cancer from SARS-CoV-2 infections. Materials and methods We extracted data regarding 9280 patients (4532 males) with laboratory-confirmed SARS-CoV-2 infection from 68 hospitals in Veneto, one of the Italian regions that was most affected by the coronavirus disease 2019 (COVID-19) pandemic. The parameters used for each COVID-19-positive patient were sex, hospitalization, admission to intensive care unit, death, tumor diagnosis, prostate cancer diagnosis, and ADT. Results There were evaluable 9280 SARS-CoV-2-positive patients in Veneto on 1 April 2020. Overall, males developed more severe complications, were more frequently hospitalized, and had a worse clinical outcome than females. Considering only the Veneto male population (2.4 million men), 0.2% and 0.3% of non-cancer and cancer patients, respectively, tested positive for SARS-CoV-2. Comparing the total number of SARS-CoV-2-positive cases, prostate cancer patients receiving ADT had a significantly lower risk of SARS-CoV-2 infection compared with patients who did not receive ADT (OR 4.05; 95% CI 1.55–10.59). A greater difference was found comparing prostate cancer patients receiving ADT with patients with any other type of cancer (OR 4.86; 95% CI 1.88–12.56). Conclusion Our data suggest that cancer patients have an increased risk of SARS-CoV-2 infections compared with non-cancer patients. However, prostate cancer patients receiving ADT appear to be partially protected from SARS-CoV-2 infections.

BACKGROUND: In East Asia, face masks are commonly worn to reduce viral spread. In Euope and North America, however, their use has been stigmatised for a long time, although this view has radically changed during the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Notwithstanding this, it is still unclear whether face masks worn by COVID-19 carriers may indeed prevent viral transmission and environmental contamination. The objective of this study was to evaluate the effectiveness of surgical face masks in filtering SARS-CoV-2. METHODS: Four male patients with COVID-19 were recruited for the study. Two patients wore a surgical mask for 5 h, while two others did not. The spread of the virus in the environment was evaluated through the approved Allplex 2019-nCoV assay. RESULTS: In the room with the two patients without surgical masks, the swab performed on the headboard and sides of the beds was positive for SARS-CoV-2 contamination. In the other room, where two patients were wearing surgical masks, all of the swabs obtained after 5 h tested negative. CONCLUSIONS: The results of the current study add to the growing body of literature supporting the use of face masks as a measure to contain the spread of SARS-CoV-2 by retaining potentially contagious droplets that can infect other people and/or contaminate surfaces. Based on the current evidence, face masks should therefore be considered a useful and low-cost device in addition to social distancing and hand hygiene during the postlockdown phase.

For survivors of severe COVID-19 disease, having defeated the virus is just the beginning of an uncharted recovery path. What follows after the acute phase of SARS-CoV-2 infection depends on the extension and severity of viral attacks in different cell types and organs. Despite the ridiculously large number of papers that have flooded scientific journals and preprint-hosting websites, a clear clinical picture of COVID-19 aftermath is vague at best. Without larger prospective observational studies that are only now being started, clinicians can retrieve information just from case reports and or small studies. This is the time to understand how COVID-19 goes forward and what consequences survivors may expect to experience. To this aim, a multidisciplinary post-acute care service involving several specialists has been established at the Fondazione Policlinico Universitario A. Gemelli IRCSS (Rome, Italy). Although COVID-19 is an infectious disease primarily affecting the lung, its multi-organ involvement requires an interdisciplinary approach encompassing virtually all branches of internal medicine and geriatrics. In particular, during the post-acute phase, the geriatrician may serve as the case manager of a multidisciplinary team. The aim of this article is to describe the importance of the interdisciplinary approach––coordinated by geriatrician––to cope the potential post-acute care needs of recovered COVID-19 patients.

Cytarabine, the 4-amino-1-(β-D-arabinofuranosyl)-2(1H)-pyrimidinone, (ARA-C) is an antimetabolite cytidine analogue used worldwide as key drug in the management of leukaemia. As specified in the manufacturers' instructions, once the components-sterile water and cytarabine powder-are unpackaged and mixed, the solution begins to degrade after 6 hours at room temperature and 12 hours at 4°C. To evaluate how to avoid wasting the drug in short-term, low-dose treatment regimens, the reconstituted samples, stored at 25°C and 4°C, were analyzed every day of the test week by reversed-phase HPLC and high-field NMR spectroscopy. All the samples remained unchanged for the entire week, which corresponds to the time required to administer the entire commercial drug package during low-dose therapeutic regimens. The drug solution was stored in a glass container at 4°C in an ordinary freezer and drawn with sterile plastic syringes; during this period, no bacterial or fungal contamination was observed. Our findings show that an cytarabine solution prepared and stored in the original vials retains its efficacy and safety and can, therefore, be divided into small doses to be administered over more days, thus avoiding unnecessary expensive and harmful waste of the drug preparation. Moreover, patients who require daily administration of the drug could undergo the infusion at home without need to go to hospital. The stability of the aliquots would help decrease hospitalization costs.

On February 20, 2020, a man living in the north of Italy was admitted to the emergency room with an atypical pneumonia that later proved to be COVID-19. This was the trigger of one of the most serious clusters of COVID-19 in the world, outside of China. Despite aggressive restraint and inhibition efforts, COVID-19 continues to increase, and the total number of infected patients in Italy is growing daily. After 6 weeks, the total number of patients reached 128,948 cases (April 5, 2020), with the higher case-fatality rate (15,887 deaths) dominated by old and very old patients. This sudden health emergency severely challenged the Italian Health System, in particular acute care hospitals and intensive care units. In 1 hospital, geriatric observation units were created, the experience of which can be extremely useful for European countries, the United States, and all countries that in the coming days will face a similar situation.

The aim of this proof-of-concept, pilot study was the evaluation of the effects of steroid administration and suspension of an inhaled corticosteroid (ICS)-long-acting β2-agonist (LABA) extrafine fixed dose combination (FDC) on metabolomic fingerprints in subjects with chronic obstructive pulmonary disease (COPD). We hypothesized that a comprehensive metabolomics approach discriminates across inhaled pharmacotherapies and that their effects on metabolomic signatures depend on the biological fluids analyzed. We performed metabolomics via nuclear magnetic resonance (NMR) spectroscopy in exhaled breath condensate (EBC), sputum supernatants, serum, and urine. Fourteen patients suffering from COPD who were on regular inhaled fluticasone propionate/salmeterol therapy (visit 1) were consecutively treated with 2-week beclomethasone dipropionate/formoterol (visit 2), 4-week formoterol alone (visit 3), and 4-week beclomethasone/formoterol (visit 4). The comprehensive NMR-based metabolomics approach showed differences across all pharmacotherapies and that different biofluids provided orthogonal information. Serum formate was lower at visits 1 versus 3 (P = 0.03), EBC formate was higher at visit 1 versus 4 (P = 0.03), and urinary 1-methyl-nicotinamide was lower at 3 versus 4 visit (P = 0.002). NMR-based metabolomics of different biofluids distinguishes across inhaled pharmacotherapies, provides complementary information on the effects of an extrafine ICS/LABA FDC on metabolic fingerprints in COPD patients, and might be useful for elucidating the ICS mechanism of action.

Objectives To assess 1-year incidence and factors related to deprescribing in nursing home (NH) residents in Europe. Design Longitudinal multicenter cohort study based on data from the Services and Health for Elderly in Long TERm care (SHELTER) study. Setting NHs in Europe and Israel. Participants 1843 NH residents on polypharmacy. Methods Polypharmacy was defined as the concurrent use of 5 or more medications. Deprescribing was defined as a reduction in the number of medications used over the study period. Residents were followed for 12 months. Results Residents in the study sample were using a mean number of 8.6 (standard deviation 2.9) medications at the baseline assessment. Deprescribing was observed in 658 residents (35.7%). Cognitive impairment (mild/moderate impairment vs intact, odds ratio [OR] 1.41, 95% confidence interval [CI] 1.11-1.79; severe impairment vs intact, OR 1.60, 95% CI 1.23-2.09), presence of the geriatrician within the facility staff (OR 1.41, 95% CI 1.15-1.72), and number of medications used at baseline (OR 1.10, 95% CI 1.06-1.14) were associated with higher probabilities of deprescribing. In contrast, female gender (OR 0.76, 95% CI 0.61-0.96), heart failure (OR 0.69, 95% CI 0.53-0.89), and cancer (OR 0.64, 95% CI 0.45-0.90) were associated with a lower probability of deprescribing. Conclusions and Implications Deprescribing is common in NH residents on polypharmacy, and it is associated with individual and organizational factors. More evidence is needed on deprescribing, and clear strategies on how to withdraw medications should be defined in the future.

Benign prostatic hyperplasia (BPH) is an age-related chronic disorder, characterized by the hyperproliferation of prostatic epithelial and stromal cells, which drives prostate enlargement. Since BPH aetiology and progression have been associated with the persistence of an inflammatory stimulus, induced both by Nuclear Factor-kappa B (NF-&kappa, B) activation and reactive oxygen species (ROS) production, the inhibition of these pathways could result in a good tool for its clinical treatment. This study aimed to evaluate the antioxidant and anti-inflammatory activity of a combined formulation of Serenoa repens and Urtica dioica (SR/UD) in an in vitro human model of BPH. The results confirmed both the antioxidant and the anti-inflammatory effects of SR/UD. In fact, SR/UD simultaneously reduced ROS production, NF-&kappa, B translocation inside the nucleus, and, consequently, interleukin 6 (IL-6) and interleukin 8 (IL-8) production. Furthermore, the effect of SR/UD was also tested in a human androgen-independent prostate cell model, PC3. SR/UD did not show any significant antioxidant and anti-inflammatory effect, but was able to reduce NF-&kappa, B translocation. Taken together, these results suggested a promising role of SR/UD in BPH and BPH-linked disorder prevention.

Proper use of inhaler devices may be problematic in elderly patients due to age-related difficulties. A survey was administered to elderly patients to investigate the usability of the Genuair® device and patients' subjective viewpoint on the device. A representative sample of the Italian population aged ≥ 65 years was completed with a pre-defined sample of 89 patients with hand arthritis/arthrosis. Of 526 respondents, 88 were not self-sufficient. Only the replies of the 438 self-sufficient respondents were analyzed. A total of 107 participants (24%) reported having respiratory diseases, and 81 of these (76%) were users of inhaler devices. After the first test, the device was considered “practical/handy” by 90% of patients and “easy to use” by 89%. After the second test, in which patients received a demonstration of the correct inhalation maneuver, the percentage of patients scoring ≥ 7 increased to 93% for the first characteristic and was confirmed for the second, with no differences between the groups in terms of age, educational level, use of devices, and presence of arthritis/arthrosis. The mean time to explain the inhaler technique and to perform a correct inhalation was 1'38"± 1'37", and 70% of the respondents required less than 2 minutes, with no differences between the groups in terms of age, education level, use of devices, and presence of arthritis/arthrosis. In conclusion, Genuair® was well accepted and easy to use in a representative sample of the Italian population aged ≥ 65 years. These characteristics make it a valid choice in the elderly, thus enabling patients to better cope with the problems and difficulties that are common to this age group.

In this paper, a seismic sensor based on the combination of ionic polymer metal composite (IPMC) and ferrofluids is presented. The device consists of a vial, filled with ferrofluid, housing an IPMC cantilever beam sensor. Considering that the behavior (e.g., frequency response) of a beam immersed in a fluid changes with the fluid density, in this paper, a novel methodology is proposed to implement a mechanism allowing for the active tuning of the sensor specifications (such as operating range, frequency behavior, and responsivity). To such aim, the addressed methodology exploits external magnetic fields to modify the density of the ferrofluid in which the IPMC sensor is immersed. A description of the sensing methodology and the realization of the sensor prototype are given along with experimental results confirming the expected behavior of the device. Moreover, a model is presented which can be used to predict the IPMC behavior as a function of the fluid properties.

The metabolic syndrome (MetS) is highly prevalent in Western older populations. MetS is an intriguing entity, because it includes potentially reversible risk factors. Some studies have suggested an inverse correlation between MetS and health-related quality of life (HRQoL), but data regarding older subjects are scanty and conflicting. The aim of this study was to assess the association between HRQoL and MetS in older, unselected community-dwelling subjects. We analyzed data of 356 subjects aged 75+ living in Tuscania (Italy). HRQoL was assessed using the Health Utilities Index, Mark 3. Diagnosis of MetS was defined according to the National Cholesterol Education Program’s ATP-III criteria. MetS was reported by 137 (38%) participants. According to linear regression analysis, MetS was associated with significantly better HRQoL in men (B = 0.19 95% CI = 0.06–0.32; p = 0.006), but not in women. Also, when the regression model was analyzed in men, MetS was associated with better HRQoL (B = 0.17, 95% CI = 0.01–0.32; p = 0.035) only among participants aged 80+. No significant associations were found in men between HRQoL and any of the single components of MetS. MetS is not associated with worse HRQoL among community-dwelling elderly; it is associated with significantly better HRQoL among the oldest men.

Summary Background & aims Cognitive impairment is a prevalent condition in older populations, independently associated with disability and mortality. Some studies have suggested a negative correlation between metabolic syndrome (MetS) and cognitive functioning, but results in older subjects are controversial. The aim of this study was to evaluate the association of cognitive performance with MetS in an older unselected population. Methods We evaluated the association of the Hodkinson Abbreviated Mental Test (AMT) score with MetS, as defined by the National Cholesterol Education Program's ATP-III criteria, in all 353 subjects aged 75+ living in Tuscania (Italy). Results MetS was positively associated with the AMT score in multivariable linear regression analysis, after adjusting (B = 0.45, 95% CI = 0.04–0.90; p = 0.03). When the same regression model was analyzed after stratifying for sex, such an association was significant in women (B = 0.76, 95% CI = 0.16–1.36; p = 0.01), but not in men. Also, when the regression model was analyzed in women, MetS was associated with better cognition (B = 1.41, 95% CI = 0.51–2.30; p Conclusions MetS is associated with better cognitive performance in community-dwelling elderly; such an association seems to depend upon the oldest female subjects.

Objectives Micro-RNAs are a group of small noncoding RNAs with modulator activity of gene expression. Recently, micro-RNA genes were found abnormally expressed in several types of cancers. To study the role of the micro-RNAs in human kidney and bladder cancer, we analyzed the expression profile of 245 micro-RNAs in kidney and bladder primary tumors. Methods and materials A total of 27 kidney specimens (20 carcinomas, 4 benign renal tumors, and 3 normal parenchyma) and 27 bladder specimens (25 urothelial carcinomas and 2 normal mucosa) were included in the study. Total RNA was used for hybridization on an oligonucleotide microchip for micro-RNA profiling developed in our laboratories. This microchip contains 368 probes in triplicate, corresponding to 245 human and mouse micro-RNA genes. Results A set of 4 human micro-RNAs (miR-28, miR-185, miR-27, and let-7f-2) were found significantly up-regulated in renal cell carcinoma (P < 0.05) compared to normal kidney. Human micro-RNAs miR-223, miR-26b, miR-221, miR-103-1, miR-185, miR-23b, miR-203, miR-17-5p, miR-23a, and miR-205 were significantly up-regulated in bladder cancers (P < 0.05) compared to normal bladder mucosa. Of the kidney cancers studied, there was no differential micro-RNA expression across various stages, whereas with increasing tumor-nodes-metastasis staging in bladder cancer, miR-26b showed a moderate decreasing trend (P = 0.082). Conclusions Our results show that different micro-RNAs are deregulated in kidney and bladder cancer, suggesting the involvement of these genes in the development and progression of these malignancies. Further studies are needed to clarify the role of micro-RNAs in neoplastic transformation and to test the potential clinical usefulness of micro-RNAs microarrays as diagnostic and prognostic tool.

The objective of this study was to optimally predict the spontaneous passage of ureteral stones in patients with renal colic by applying for the first time support vector machines (SVM), an instance of kernel methods, for classification. After reviewing the results found in the literature, we compared the performances obtained with logistic regression (LR) and accurately trained artificial neural networks (ANN) to those obtained with SVM, that is, the standard SVM, and the linear programming SVM (LP-SVM); the latter techniques show an improved performance. Moreover, we rank the prediction factors according to their importance using Fisher scores and the LP-SVM feature weights. A data set of 1163 patients affected by renal colic has been analyzed and restricted to single out a statistically coherent subset of 402 patients. Nine clinical factors are used as inputs for the classification algorithms, to predict one binary output. The algorithms are cross-validated by training and testing on randomly selected train- and test-set partitions of the data and reporting the average performance on the test sets. The SVM-based approaches obtained a sensitivity of 84.5% and a specificity of 86.9%. The feature ranking based on LP-SVM gives the highest importance to stone size, stone position and symptom duration before check-up. We propose a statistically correct way of employing LR, ANN and SVM for the prediction of spontaneous passage of ureteral stones in patients with renal colic. SVM outperformed ANN, as well as LR. This study will soon be translated into a practical software toolbox for actual clinical usage.

A genetic component in prostate cancer (PCa) has been recognized for decades, and much evidence has been accumulated in favor of a significant, but heterogeneous hereditary component in PCa. Purpose We studied the incidence of the familial and hereditary forms of PCa in our population of patients with a diagnosis of PCa clinically localized and age at diagnosis Results A positive family history for PCa was found in 72 patients (14.4%). In 15 patients (3%), we observed a hereditary form of PCa and in 57 patients (11.4%) a familial form. Patients with hereditary PCa had a lower age at diagnosis (55 yrs). Genealogical pedigrees ruled out mendelian dominant autosomical transmission. No difference was found in the preoperatory, clinical and pathological features among the three PCa groups. A statistically significant familial association was found between PCa and cancer of breast and uterus. Conclusions This study supports evidence of a hereditary predisposition to PCa and the suggestion that an excess familial risk of PCa is due to the inheritance of multiple moderate-risk genetic variants.

The aim of this study is to evaluate the role of an extensive “saturation biopsy” in patients at increased risk for prostate cancer with previously negative biopsies, HGPIN or ASAP diagnosis. Materials and Methods We performed an extensive 24 cores biopsy with spinal anaesthesia in 168 patients with at least 1 prior negative biopsy and persistently high PSA and/or abnormal digital rectal examination or with a ASAP or HGPIN diagnosis at previous biopsy. Results A total of 55 patients were diagnosed having prostate cancer for an overall diagnostic yeld of 33 %. Specifically, cancer was detected in 79% of ASAP, 32% of HGPIN and 28% of prior negative biopsies. 31 patients underwent radical retropubic prostatectomy. There was no correlation between number of positive biopsy cores and pathological stage or pathological Gleason score. A high concordance was found between clinical and pathological Gleason score. Conclusions Extensive biopsy can be considered a safe and effective diagnostic tool in men at risk for prostate cancer with previous negative biopsies. This procedure comes out to be particularly useful also in patients with a prior ASAP or HGPIN.

To evaluate the prognostic significance of different detection modalities of renal cell carcinoma (RCC) in a large cohort of patients who had been previously submitted to surgery in two teaching hospitals in Italy.We reviewed the clinical records of 1446 patients who had been submitted to surgical treatment for RCC at the Departments of Urology of Padua (n=747) and Verona (n=699) from 1976 to 2000. Patients were classified into two groups according to the detection mode: symptomatic and incidental. The cancer-specific survival probability was estimated according to the Kaplan-Meier method. In order to compare the survival curves the log rank test was used. The predictive independent value of the variables was examined using the Cox proportional hazards model.Six hundred and thirty patients (43.6%) were treated for incidental RCC and 816 (56.4%) for symptomatic RCC. In the incidental group, the size (p0.001), the pathological stage (p0.001) and the nuclear grading (p0.001) of tumors were lower than those causing symptoms. The 5-year and 10-year cancer-specific survival probability were 84% and 75% in the incidental group, and 66% and 54.5% in the symptomatic group (p0.0001), respectively. At a multivariate analysis, the mode of detection was an independent predictive variable (H.R. 1.559), as well as pathological stage (H.R. 1.809), nuclear grading (H.R. 1.411), sizeor=4 cm (H.R. 1.667), and venous involvement (H.R. 1.526).In patients with RCC, the detection modality can predict the cancer-specific survival rate independently of tumor pathological stage and grading.

Objectives: Prostatic biopsy is a minor diagnostic procedure; despite the simplicity of execution this procedure can determine a high patients' discomfort. Methods: We analyzed the experience reported in the literature concerning the pain and the anxiety, the role of local or intrarectal anesthesia and the complications related to prostatic biopsy. Key words used for the Medline search included: prostate cancer, biopsy, transrectal ultrasound anesthesia, complications. Results: The reduction of patients' pre biopsy anxiety may help the physician to perform a better prostate biopsy. While the use of pre biopsy enemas seems questionable, the use of antibiotic prophylaxis is mandatory when the biopsy is transrectal and could be useful if the approach is transperineal. The use of anaesthesia (periprostatic local injection of lidocaine or intrarectal administration of lidocaine gel) seems to reduce patients' discomfort. The higher is the number of biopsy cores, the greater is the need for anaesthesia. Conclusions: Trans-rectal ultrasound (TRUS) prostatic biopsy with a correct patient's preparation has a limited impact on patient's well-being.

BACKGROUND There is presently no effective therapy for relapsing, metastatic, androgen-independent prostate cancer. Immunotherapy with monoclonal antibody–vehicled toxins (Immunotoxins, ITs) may be a promising novel treatment option for the management of prostate cancer in these cases. METHODS Three anti–prostate specific membrane antigen (anti-PSMA) monoclonals (J591, PEQ226.5, and PM2P079.1) were cross-linked to ricin A-chain (RTA; native or recombinant), and their cytotoxic effects were investigated in monolayer and three-dimensional (3-D) cell cultures of prostate carcinoma cells (LNCaP). RESULTS The various Immunotoxins showed effects in the nanomolar range (IC50s of 1.6–99 ng/ml) against PSMA+ cells (IC50 being the concentration inhibiting 50% cell proliferation or protein synthesis). PSMA− cell lines were 62- to 277-fold less sensitive to anti-PSMA ITs, evidencing an appreciable therapeutic window. Treatment with J591-smpt-nRTA (0.35–31.7ng/ml) resulted in complete eradication of 3-D tumor micromasses or in 1.46- to 0.35-log reduction of target cells number, depending on the dose. CONCLUSION Anti-PSMA ITs appear to be promising for use in the eradication of small prostate tumor cell aggregates present in tissues and in the bone marrow. Prostate 53: 9–23, 2002. © 2002 Wiley-Liss, Inc.

Introduction: Intravesical epirubicin is a widely used agent for the treatment of superficial bladder cancer. A direct relationship between dose and activity has been reported: unfortunately the dose increase also increased the frequency and the intensity of treatment-related side effects. Materials and Methods: A phase 2 trial was designed to evaluate the toxicity and the activity of a delayed (biweekly) high-dose (80 mg) epirubicin therapy of superficial bladder cancer. Thirty patients with intermediate risk superficial bladder cancer (stage mTa, G2) have been treated with transurethral resection and epirubicin intravesical therapy: the patients were given 80 mg epirubicin in 50 ml sterile saline every 2 weeks for 6 times (delayed regimen). The follow-up ranged from 3 to 26 months. Eleven of 30 (37%) patients experienced a local adverse reaction to intravesical epirubicin requiring specific medication (grade ≧2 according to NCI-CTC v.2.0, 1999). No systemic toxicity related to the treatment was observed. Results: Out of the 29 evaluable patients, 22 (76%) were free of disease after the induction course, 6 (21%) had superficial bladder cancer recurrences and 1 (3%) experienced tumor progression. Conclusion: A delayed (biweekly instillation) high-dose (80 mg) intravesical epirubicin regimen was acceptable in terms of side effects and showed a worthwhile therapeutical impact in patients with intermediate risk superficial bladder cancer.

We present the unusual case of a 76-year-old male who developed an intestinal recurrence of the same tumor 5 years after hepatic resection for an intrahepatic cholangiocarcinoma. At the time of the first surgery, the patient had undergone hepatic bisegmentectomy of segments IV and V with an 'en bloc' gallbladder resection and porta hepatis lymphadenectomy for the presence of a focal cholangiocarcinoma measuring about 3.0 x 2.5 cm in diameter. The histological report confirmed intrahepatic cholangiocarcinoma, the resection margins were free from disease, and there were no lymph node metastases. Five years later colonoscopy showed, at the level of the splenic flexure, the presence of a sessile bilobate polypoid neoplasm. The patient underwent left hemicolectomy with a histological diagnosis of an isolated recurrence of cholangiocarcinoma.

ObjectiveTo investigate possible differences between Italian and Swedish men in health-related quality of life (HRQL) after cystectomy and orthotopic bladder substitution for bladder cancer. Patients and methodsThirty-three men in Padua, Italy and 33 in Lund, Sweden were assessed after respective mean postoperative periods of 42 and 52 months. Three questionnaires were used: (i) dealing with view-of-life issues; (ii) the core questionnaire QLQ-C30(+3) from the European Organization for Research and Treatment of Cacncer, with added questions on urinary symptoms and sexuality; and (iii) one focusing on postoperative psychosocial and sexual adjustment. ResultsWhile Italian and Swedish men did not differ in their central values, they differed significantly in belief-related values, such as religion. Urinary prob-lems and erectile dysfunction were common in both groups, the former possibly commoner in the Swedish men and the latter in the Italians. Changes in mood and self-esteem were common in both groups. On a visual analogue scale, the Italian men reported a worse present mood than the Swedish men, but expressed a more favourable outlook on their future. ConclusionDespite differences in philosophical attitudes between Italian and Swedish men, there were no major differences in HRQL. Caution is required in interpreting these findings because there were few participants and the possible inadequacy of the methods used to evaluate the complex concept of quality of life.

To determine if body mass index (BMI = weight/height2), predictive of mortality in seriously ill hospitalized and institutionalized patients, is also predictive of mortality in a longitudinal epidemiologic study.A prospective cohort study.Rovereto, a town in northern Italy.A consecutive sample of 214 patients aged 81.2 +/- 7.3 years receiving community care services.Malnutrition and mortality.According to logistic regression analysis, malnutrition status, expressed by a BMI22 Kg/m2, was correlated with dependency in Activity of Daily Living (odds ratio 1.21; 95% confidence interval (CI) 1.01-1.45). Only a low BMI was associated with 1-year survival in Cox regression analysis, after adjusting for potential confounders (relative risk 0.85; 95%CI, 0.74-0.97). A high BMI (27 Kg/m2) was not significantly related to risk of mortality.Nutrition variables are a cardinal component of comprehensive geriatric assessment. Our results suggest that BMI, a simple anthropometric measure of nutritional status, is an important predictor of mortality among older people living in the community. Even when controlling for clinical and functional variables, a low BMI remained a significant and independent predictor of shortened survival.

Pathological predictors of outcome for patients undergoing radical cystectomy for bladder cancer are needed as few data are available in the literature. We retrospectively analyzed a homogeneous and contemporary series of patients treated with radical surgery as monotherapy for bladder cancer to identify the independent predictors of survival.We evaluated 369 of 535 patients with bladder cancer treated with radical cystectomy, pelvic node dissection and urinary diversion by the same staff at a single institution between February 1982 and February 1994. Patients treated with radiation therapy and/or chemotherapy, and those who did not undergo formal pelvic node dissection were excluded from study. The end point of univariate and multivariate analyses was the overall 5-year survival.Univariate analysis revealed that tumor stage, nodal involvement, ureteral obstruction, and vascular, lymphatic and perineural invasion were prognostic predictors of survival (p0.05). However, only tumor stage (p0.0000) and nodal involvement (p0.0000) were independent prognostic variables of survival on multivariate analysis.Tumor stage and nodal involvement are the only independent predictors of survival to be used to select the optimal therapy after radical cystectomy, stratify patients in controlled trials and evaluate new prognostic factors.

Objective: To compare the BTA statTM test (BTA stat), a new one-step immunochromatographic assay that can be performed in the urologist’s office or in the laboratory, to

The likelihood of finding organ-confined untreated prostate cancer (PCa) by pathological examination at the time of radical prostatectomy (RP) is only 50% in patients with clinically organ-confined disease. In addition, tumour is present at the resection margin in approximately 30% of clinical T2 (clinical stage B) cases. The issue of clinical "understaging" and of resection limit positivity have led to the development of novel management practices, including "neoadjuvant" hormonal therapy (NHT). The optimal duration of NHT is unknown. We undertook the present analysis to evaluate the effect of NHT on pathologic stage of PCa and resection limit status in patients with prostate cancer and treated with total androgen ablation either for three or six months before RP. Between January 1996 and February 1998, 259 men with prostate cancer underwent radical retropubic prostatectomy and bilateral pelvic node dissection in the 26 centres participating in the Italian randomised prospective PROSIT study. Whole mount sectioning of the complete RP specimens was adopted in each centre for accurately evaluating the pathologic stage and resection limit status. By February 1998, haematoxylin and eosin stained sections from 155 RP specimens had been received and evaluated by the reviewing pathologist (RM). 64 cases had not been treated with total androgen ablation (e.g. NHT) before RP was performed, whereas 58 and 33 had been treated for three and six months, respectively. 114 patients were clinical stage B whereas 41 were clinical stage C. After three months of total androgen ablation, pathological stage B was more prevalent among patients with clinical B tumours, compared with untreated patients (57% in treated patients vs. 36% in untreated). The percentage of cancers with negative margins was statistically significantly greater in patients treated with neoadjuvant therapy than those treated with immediate surgery alone (69% vs. 42%, respectively). After six months of NHT therapy the proportion of patients with pathological stage B (67% vs. 36%, respectively) and negative margins was greater than after 3 months (92% vs. 42%, respectively). For clinical C tumours, the prevalence of pathological stage B and negative margins in the patients treated for either 3 or 6 months was not as high as in the clinical B tumours, when compared with the untreated group (pathological stage B: 31% and 33% vs. 6% in the clinical C cases, respectively. Negative margins: 56% and 67% vs. 31%, respectively). The initial results of this study suggest that total androgen ablation before RP is beneficial in men with clinical stage B because of the significant pathological downstaging and decrease in the number of positive margins in the RP specimens. These two effects are more pronounced after six months of NHT than after three months of therapy. The same degree of beneficial effects are not observed in clinical C tumours.

Objectives: to compare the adequacy of nutritional support in surgical, medical and geriatric wards, and to assess correlates and prognostic implications of inadequate caloric intake. Design: prospective observational study. Setting: an acute-care university hospital. Patients: 370 patients over 70 years of age consecutively admitted to general surgery (n = 86), general medicine (n = 149) and geriatric (» = 135) wards. Method: a multidimensional assessment was performed on admission, and the average daily caloric intake was computed. The logistic regression analysis was used to characterize patients at risk of starvation, defined as a caloric intake below 40% of the estimated requirement, and of death. Results: the average daily caloric intake, expressed as mean ± SD, was 63 ± 40%, 63 ± 31% and 69 ± 34% of that required in surgical, medical and geriatric wards, respectively. Patients at risk of starvation were identified by body mass index

Transplanted patients frequently present erectile impotence. In order to test any interference by cyclosporine A (CsA), which is commonly used in the post-transplantation management, we investigated the in vitro contractile and relaxant responses of corpus cavernosum and aorta from rabbits chronically treated with CsA. Male New Zealand White rabbits 6 months of age were treated with CsA (25 mg/kg per day s.c.) or solvent (corn oil) for 3 weeks. Descending thoracic aorta and erectile tissue were studied in vitro at the end of treatment. Isometric tension was recorded. In thoracic aorta, noradrenaline (0.1-30 mM) induced a concentration-dependent contraction with no difference between the two groups. Acetylcholine (30 nM-3 mM) produced relaxation (52 +/- 4% at 1 mM) that was significantly reduced in comparison to controls (67 +/- 4%, P0.05). ATP (3-10 mM) relaxation was not significantly different (maximal 78 +/- 10% and 62 +/- 12% in CsA-treated and controls). The relaxation produced by sodium nitrite was reduced in CsA-treated rabbits (at 10 mM and 0.1 mM concentrations). In erectile tissue, no significant variation in the response of isolated erectile tissue to the above drugs was observed between CsA-treated and control animals. These data indicate that chronic treatment with CsA in rabbits, despite alteration of the in vitro response of thoracic aorta, does not directly influence the function of penile tissue with relaxants.

A series of patients with concurrent transitional cell carcinoma involvement of the prostate and bladder is reviewed to define the impact of prostate involvement pathways and the degree of prostate invasion on survival rate.A total of 72 patients who underwent radical cystectomy for pathological stage pT4a (D1) cancer was divided into contiguous--stage pT4a, transitional cell carcinoma of the bladder extended into the prostate through the bladder wall and noncontiguous--stage pT4a simultaneous transitional cell carcinoma of the prostate and bladder carcinoma that did not directly infiltrate into the prostate through the bladder wall. In the latter group the degree of prostate invasion was classified as urethral mucosal involvement, ductal/acinar involvement, stromal invasion and extracapsular extension. The survival rate was estimated by the Kaplan-Meier and Cox proportional hazards methods. Comparisons between curves were performed by univariate log rank and multivariate L-ratio tests.The overall 5-year survival rate for stage pT4a was 21.5% (median followup 64 months). Furthermore, 46% and 7% of patients in noncontiguous and contiguous pT4a groups, respectively, were estimated to be alive (p0.000). Those with positive nodes experienced a poor outcome in both groups. Of patients with noncontiguous pT4a stage 100% with urethral mucosal involvement, 50% with ductal/acinar involvement and 40% with stromal invasion were estimated to be alive. The major prognostic factors were bladder tumor stage, nodal involvement and degree of prostate invasion.The invasion pathways of the prostate in patients with transitional cell bladder carcinoma have a statistically significant prognostic role. Contiguous and noncontiguous involvements are 2 distinct clinicopathological features and they should not be included in the same stage. In the noncontiguous stage pT4a group bladder and prostate transitional cell carcinoma should be separately staged, and prostate involvement also should be staged according to invasion degree.

Objective : Bellini duct carcinoma (BDC) is a rare and highly aggressive renal tumor whose histogenesis is still a matter of debate although a putative origin from collecting ducts has been proposed. Methods : A primary tumor cell culture was obtained from a BDC of a 57-year-old man who presented with a mass of the right kidney. The patient died from disease progression 18 months after diagnosis. The light and ultrastructural features were consistent with previous reports on BDC. The expression of low (Ker 18) and high (Ker 5, Ker 8, Ker 10) molecular weight keratins was studied. Results : The BDC tumor cells displayed strong positivity for keratins, 5, 8 and 18 but did not react with the anti-keratin 10 antibody. Northern blot analysis of total mRNA revealed expression of the c-erbB- I oncogene unlike two conventional clear cell carcinomas of the kidney used as control. Cytogenetic analysis revealed an aneuploid karyotype : 53, XY, del(1)(p34), +iso(1q), +iso(5p), +4, +7, +8, -14, del(16)(q22), +17,-18,+20,+20,-22. No submicroscopic deletion on p14-21 and p26 regions of the short arm of chromosome 3 was detected on Southern blot analysis. Conclusions : The absence of structural changes in the short arm of chromosome 3 (usually present in hereditary and sporadic renal cell carcinomas) in the presence of chromosomal abnormalities observed in malignant lesions of urothelial origin confers to BDC a unique genetic profile among papillary tumors of the kidney.

Several clinical trials have shown intravesical bacillus Calmette-Guerin (BCG) to be effective in the prophylaxis of papillary tumour recurrences and in the therapy of bladder carcinoma in situ (CIS), as well as in delaying progression to muscle invasion. Nevertheless, the optimal regimen of BCG therapy for superficial bladder cancer has still to be defined. In a previous phase II trial, a low-dose regimen (BCG Pasteur strain, 75 mg) was able to achieve clinically significant response rates with a decrease in side-effects compared with other reported studies using standard-dose BCG. However, a phase III randomized trial - low dose versus standard dose (BCG Pasteur strain, 75 vs. 150 mg) - was considered necessary to clarify definitively the relationships between dose, efficacy and toxicity. The results of the interim analysis of 183 patients (performed in 1993) have shown response rates to be better in patients submitted to a low-dose BCG regimen (p=0.0009) and a significant decrease in most of the common side-effects (cystitis, fever, haematuria; p

Intravesical Bacillus Calmette-Guérin (BCG) is the gold standard treatment for intermediate and high-risk non-muscle-invasive bladder cancer. BCG therapy is the most successful example of immunotherapy in cancer. Unfortunately, the treatment-related side effects are still relevant. Furthermore, non-responder patients are candidate to radical cystectomy in the absence of valuable alternative options. These aspects have prompted the search for newer biological response modifiers (BRM) with a better benefit/side effects ratio. The toll-like receptor (TLR) 2 ligand, Helicobacter pylori protein HP-NAP, has been shown to deserve a potential role as BRM. HP-NAP is capable of driving the differentiation of T helper (Th) 1 cells, both in vitro and in vivo, because of its ability to create an IL-12-enriched milieu. Herein, we report that local administration of HP-NAP decreases tumour growth by triggering tumour necrosis in a mouse model of bladder cancer implant. The effect is accompanied by a significant accumulation of both CD4+ and CD8+ IFN-γ-secreting cells, within tumour and regional lymph nodes. Noteworthy, HP-NAP-treated tumours show also a reduced vascularization due to the anti-angiogenic activity of IFN-γ induced by HP-NAP. Our findings strongly indicate that HP-NAP might become a novel therapeutic "bullet" for the cure of bladder tumours.

Purpose Patients with non-muscle invasive bladder cancer recurrence after 2 induction courses of BCG are eligible for radical cystectomy. So, in the last years research to discover new drugs for the management of non-muscle invasive bladder cancer recurrence after failure of first and second line therapy is ongoing. In accordance to the results obtained with BCG, whose mechanism depends on the induction of the T helper 1 (TH1) immune response, we investigated the activity of a Toll-like receptor (TLR) 2 ligand, named Helicobacter Pylori Neutrophil Activating Protein (HP-NAP), that we recently demonstrated being able of enhancing the differentiation of Th1 cells, both in vitro and in vivo, because of its ability to create an IL-12 enriched milieu. Materials and Methods We show here, in a mouse model of bladder neoplasm implants, that local administration of HP-NAP decreases tumor growth by inducing tumor necrosis. Results The result is joined up with a massive cluster of both CD4+ and CD8+ IFN-γ+ cells, within neoplasm and regional lymph nodes. It is of note that HP-NAP-treated tumors show also a reduced vascularization due to the anti-angiogenic activity of IFN-γ induced by HP-NAP. Conclusions The present study suggests that the activity of HP-NAP against urothelial tumor burden warrants subsequent in vivo studies.

The process of design and development of virtual environments can be supported by tools and frameworks, to save time in technical aspects and focusing on the content. In this paper we present an academic framework which provides several levels of abstraction to ease this work. It includes state-of-the-art components we devised or integrated adopting open-source solutions in order to face specific problems. Its architecture is modular and customizable, the code is open-source., Comment: 12 pages, 1 figure, Proceedings of the 4th International ICST Conference On Intelligent Technologies For Interactive Entertainment, 2011

Storing data in the cloud poses a number of privacy issues. A way to handle them is supporting data replication and distribution on the cloud via a local, centrally synchronized storage. In this paper we propose to use an in-memory RDBMS with row-level data encryption for granting and revoking access rights to distributed data. This type of solution is rarely adopted in conventional RDBMSs because it requires several complex steps. In this paper we focus on implementation and benchmarking of a test system, which shows that our simple yet effective solution overcomes most of the problems., 8 pages, 8 figures

We report the preliminary results of laser lithotripsy of cystine stones accomplished in 2 patients with the use of a new method of photosensitization. Transurethral rigid ureterorenoscopy was performed with an 8.5F instrument to reach 0.8 and 1.8 cm. stones located in the right and left lumbar ureters, respectively. A 320 mu. fiber was then inserted and pushed into contact with the stone. Then, 400 preliminary impulses were released from a pulsed dye laser (504 nm) with energy output at 140 mJ. and at a rate of 5 Hz. without any visible modification of the stone structure. The saline solution used as irrigation fluid was then substituted with a 2% solution of rifamycin. Totals of 95 and 152 impulses released at the same energy output previously used were then sufficient to produce a satisfactory fragmentation of the stone in both cases. Sonography and excretory urography showed no alterations of the treated urinary tract in either case. The use of rifamycin in the irrigation fluid is suggested for laser treatment of hard or nonabsorbent stones, since this substance favors optical coupling and lowers the threshold of plasma formation on the surface of the stone.

In the first part of our experience approximately 300 stones of different composition have been treated in vitro with three different laser sources: Nd-YAG laser (1,064 nm), dye laser (504 nm) and alexandrite laser (755 nm). Calcium oxalate monohydrate and brushite stones appeared to be the most resistant to lithotripsy. Highest fragmentation rates were obtained for calcium oxalate dihydrate stones followed by struvite, uric acid and hydroxyapatite stones. The Nd-YAG laser did not appear to be ideal for lithotripsy since early damage to the fiber tip was observed when this source was used. Both the dye and the alexandrite lasers were almost always effective in fragmenting the various types of stones. We subsequently treated some cystine stones while immersed in water or in solutions of carmine indigo (2%), methylene blue (5%), rifamycin (0.6 and 6%) and rifampicin (0.8 and 0.3%) with the dye or the alexandrite laser. The spectra of these solutions, previously analyzed with the spectrophotometer, showed that rifamycin and rifampicin absorbed large amounts of light radiation at the wave length of the dye laser (504 nm). Successful fragmentation occurred only when the dye laser was used to treat stones immersed in the more concentrated solutions of these two substances. The quantity of fragmented material after treating a 10-cm3 cystine stone previously immersed in the more concentrated solutions of rifamycin and rifampicin (30 and 10 mm3, respectively) confirmed previous results.(ABSTRACT TRUNCATED AT 250 WORDS)

This work presents the design and implementation of our Browser-based Massively Multiplayer Online Game, Living City, a simulation game fully developed at the University of Messina. Living City is a persistent and real-time digital world, running in the Web browser environment and accessible from users without any client-side installation. Today Massively Multiplayer Online Games attract the attention of Computer Scientists both for their architectural peculiarity and the close interconnection with the social network phenomenon. We will cover these two aspects paying particular attention to some aspects of the project: game balancing (e.g. algorithms behind time and money balancing); business logic (e.g., handling concurrency, cheating avoidance and availability) and, finally, social and psychological aspects involved in the collaboration of players, analyzing their activities and interconnections., 8 pages, 6 figures; SIMUTools '10: Proceedings of the 3rd International ICST Conference on Simulation Tools and Techniques

Subjects with depression might request more healthcare services. The aim of this study was to evaluate the association of depressive symptoms with hospitalization and mortality rates in a general unselected older population.We assessed the association of the 30-items Geriatric Depression Scale (GDS) score with one-year hospitalization and mortality in all 344 subjects aged 75+ living in Tuscania (Italy). This population had been enrolled in a national study of the genetic determinants of health status. Analyses were conducted using continuous, as well as categorical GDS score levels.After adjusting for potential confounders, depressive symptoms were associated in Cox regression modelling with hospitalization (relative risk, RR = 1.05; 95% confidence interval, CI = 1.01-1.09; p = 0.016), but not with mortality (RR = 1.06; 95% CI = 0.96-1.16; p = 0.246). Increasing GDS score levels were associated with increasing risk of hospitalization (p for trend = 0.033). Up to 39% of hospitalizations might be attributed to depression.Depressive symptoms are not associated with increased mortality rates in general older populations. However, depressive symptoms represent a potentially reversible determinant of increased hospitalization rates in these subjects, independent of the presence and severity of other medical conditions.